HF158K1 in Patients With HER-2 Expressing Advanced Solid Tumors

A Phase 1 Clinical Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of HF158K1 in Participants With HER-2 Expressing Advanced Solid Tumors

HF158K1 is an investigational liposome form of doxorubicin hydrochloride, an anthracycline topoisomerase inhibitor, encapsulated by lipid membranes containing TL01, a HER2-directed Trastuzumab Fab fragment conjugated lipid.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumors, Adult
• Intervention / Treatment: Drug: HF158K1 / 1.4 g lipid dose; Drug: HF158K1 / 2.2 g lipid dose; Drug: HF158K1 / 2.9 g lipid dose

Detailed Description

This study is a multi-regional, open-label, multiple-dose administration dose-escalation and dose-expansion study, including a Dose-Escalation Phase (Ia) and a Dose-Expansion Phase (Ib).

HF158K1 contains multiple copies of the targeting antibody on liposome surface. It is designed to bind and deliver the chemotherapeutic doxorubicin to tumor cells at even very low HER2 expression levels. The study recruits patients with unresectable or metastatic advanced solid tumors (HER-2 positive (IHC 3+, or IHC 2+ with ISH +) or HER-2 low expression (IHC 2+ with ISH -, or IHC 1+)) who have failed or are intolerant (disease progression, or intolerance to chemotherapy, targeted therapy, etc.) to standard treatment, or currently have no available treatment regimen.

Phase 1a(Dose escalation) will assess the safety，tolerability，pharmacokinetics of HF158K1 in participants to determine the maximum tolerated dose (MTD) of HF158K1 through the incidence of dose-limiting toxicity (DLT).

Phase 1b (Dose bridging) will be conducted in Chinese patients to bridge the safety and pharmacokinetic data between different ethnic populations.

Phase 1c(Dose expansion) will assess safety and preliminary efficacy of HF158K1 in participants with specific tumor types in selected dose groups.

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yongfeng Huang; Phone Number: +86-13916925827; Email: huangyf@hf-biopharm.com
• Study Contact Backup: Name: Xun Wang; Phone Number: +86-16687323386; Email: wangxun21@hf-biopharm.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Not yet recruiting
      • Sun yat-sen University Cancer Center
      • Principal Investigator: Kai Yao
      • Contact: Kai Yao, PhD; Email: yaokai@sysucc.org.cn
• United States
  • Texas
    • Dallas, Texas, United States, 75241
      • Recruiting
      • Mary Crowley Cancer Research
      • Contact: MINAL BARVE; Phone Number: 972-566-3000; Email: MBarve@MaryCrowley.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary to participate and sign ICF.
2. Age ≥ 18 and ≤ 75 years.
3. Unresectable or metastatic advanced solid tumors with HER-2 expression (IHC 3+, 2+, or 1+).
4. ECOG score 0-1.
5. Expected survival ≥ 6 months.
6. At least one measurable lesion per RECIST v1.1.
7. Adequate organ function: ANC ≥ 1.5×10⁹/L, LYM ≥ 1.0×10⁹/L, PLT ≥ 90×10⁹/L, HGB ≥ 8.0 g/dL; APTT ≤ 1.5×ULN, INR ≤ 1.5; TBIL ≤ 1.5×ULN, ALT/AST ≤ 2.5×ULN (≤ 5×ULN if liver metastases); CrCl ≥ 30 mL/min; LVEF ≥ 50%.
8. Agreement to use effective contraception.

Exclusion Criteria:

1. Cumulative doxorubicin dose ≥ 350 mg/m² or prior anthracycline-induced cardiotoxicity.
2. Current use of immunosuppressants or systemic corticosteroids (> 10 mg/day prednisone).
3. Prior anti-tumor therapy < 2 weeks (4 weeks for nitrosourea/mitomycin C).
4. Symptomatic CNS metastases.
5. Unresolved AEs from prior therapy > Grade 1.
6. Serious cardiovascular diseases (thromboembolic events within 3 months, NYHA III-IV, ACS within 6 months, or uncontrolled hypertension).
7. Active infection or unexplained fever > 38.5°C.
8. HIV, active HBV or HCV.
9. Pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation: HF158K1 1.4 g lipid dose; Participants in this dose group (1.4 g lipid dose) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.	Drug: HF158K1 / 1.4 g lipid dose; Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.; Other Names: Infusion
Experimental: Dose escalation: HF158K1 2.2 g lipid dose; Participants in this dose group (2.2 g lipid dose) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.	Drug: HF158K1 / 2.2 g lipid dose; Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.; Other Names: Infusion
Experimental: Dose escalation: HF158K1 2.9 g lipid dose; Participants in this dose group (2.9 g lipid dose) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.	Drug: HF158K1 / 2.9 g lipid dose; Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.; Other Names: Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	Defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0)	The period of AE collection starts after the participant receives the investigational drug, until 28±3 days after the EOT/early withdrawal or before the participant starts another anti-tumor treatment (whichever occurs first).
Incidence of dose-limiting toxicities(DLT)	Observe the dose limiting toxicity, and Incidence of dose-limiting toxicities(DLT) will be assessed	The DLT evaluation period is from the first administration of the investigational drug to the end of the first treatment cycle, lasting for 21 days.（only Ia）
Determine the maximum tolerated dose	The dose at which the incidence of DLT was closest to the target probability of toxicity (30%).	The first administration of the investigational drug to the end of the first treatment cycle, lasting for 21 days.
Red blood cell count in whole blood sample	Changes from baseline for Red blood cell count in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
White blood cell in whole blood sample	Changes from baseline for white blood cell count in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Hematocrit in whole blood sample	Changes from baseline for Hematocrit in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Neutrophil count in whole blood sample	Changes from baseline for neutrophil count in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Hemoglobin concentration in whole blood sample	Changes from baseline for hemoglobin concentration in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Percentage of lymphocytes (LYM%)	Changes from baseline for Percentage of lymphocytes (LYM%) in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Lymphocyte count	Changes from baseline for Lymphocyte count in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Percentage of neutrophils (NEU%) Percentage of neutrophils (NEU%)	Changes from baseline for Percentage of neutrophils (NEU%) in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Platelet count in whole blood sample	Changes from baseline for Platelet count in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Prothrombin time in whole blood sample	Changes from baseline for Prothrombin time in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
International normalized ratio in whole blood sample	Changes from baseline for international standardized ratio in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Fibrinogen in whole blood sample	Changes from baseline for Fibrinogen in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Activated partial prothrombin time in whole blood sample	Changes from baseline for activated partial thromboplastin time in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Total bilirubin concentration in whole blood sample	Changes from baseline for total bilirubin concentration in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
ALT concentration in whole blood sample	Changes from baseline for alanine aminotransferase(ALT) concentration in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
AST concentration in whole blood sample	Changes from baseline for aspartate aminotransferase(AST) concentration in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Total protein concentration in whole blood sample	Changes from baseline for total protein concentration in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Urea concentration in whole blood sample	Changes from baseline for urea concentration in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Creatinine concentration in whole blood sample	Changes from baseline for creatinine concentration in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Total cholesterol concentration in whole blood sample	Changes from baseline for total cholesterol concentration in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Triglycerides concentration in whole blood sample	Changes from baseline for triglycerides concentration in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
HDL-C in whole blood sample	Changes from baseline for high density lipoprotein cholesterol (HDL-C) in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
LDL-C in whole blood sample	Changes from baseline for low density lipoprotein cholesterol (LDL-C) in whole blood sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Glucose in whole blood sample	Changes from baseline for Lactic dehydrogenase in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Alkaline phosphatase in whole blood sample	Changes from baseline for Lactic dehydrogenase in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Lactic dehydrogenase in whole blood sample	Changes from baseline for Lactic dehydrogenase in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Gamma-glutamyl transferase in whole blood sample	Changes from baseline for Gamma-glutamyl transferase in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Albumin in whole blood sample	Changes from baseline for Albumin in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Direct bilirubin in whole blood sample	Changes from baseline for Direct bilirubin in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Sodium in whole blood sample	Changes from baseline for Sodium in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Potassium in whole blood sample	Changes from baseline for Potassium in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Chloride in whole blood sample	Changes from baseline for Chloride in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Calcium in whole blood sample	Changes from baseline for Calcium in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Phosphate in whole blood sample	Changes from baseline for Phosphate in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Uric acid in whole blood sample	Changes from baseline for Uric acid in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Creatine kinase in whole blood sample	Changes from baseline for Creatine kinase in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Creatine kinase isoenzyme in whole blood sample	Changes from baseline for Creatine kinase isoenzyme in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Troponin-T (TnT) in whole blood sample	Changes from baseline for Troponin-T in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Troponin-I (TnI) in whole blood sample	Changes from baseline for Troponin-I in whole blood	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Urine protein in urine sample	Changes from baseline for Urine protein in urine sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Red blood cells in urine sample	Changes from baseline for Red blood cells in urine sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
White blood cells in urine sample	Changes from baseline for White blood cells in urine sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
PH in urine sample	Changes from baseline for pH in urine sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Ketone bodies in urine sample	Changes from baseline for Ketone bodies in urine sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Urine glucose in urine sample	Changes from baseline for Urine glucose in urine sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Urine bilirubin in urine sample	Changes from baseline for Urine bilirubin in urine sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Urine occult blood in urine sample	Changes from baseline for Urine occult blood in urine sample	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Heart Rate in beats per minute in beats per minute of ECG	Changes from baseline for heart rate in beats per minute	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
RR Interval by ECG	Changes from baseline for RR interval by ECG	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
PR Interval by ECG	Changes from baseline for PR interval by ECG	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
QRS Interval by ECG	Changes from baseline for QRS interval by ECG	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
QT Interval by ECG	Changes from baseline for QT interval by ECG	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
QTcF by ECG	Changes from baseline for QTcF interval by ECG	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Left ventricular ejection fraction measured by Echocardiography	Changes from baseline for Left ventricular ejection fraction measured by Echocardiography	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Body (Ear) Temperature measurement in Vital Signs	Changes from baseline for Body (Ear) Temperature	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Pulse measurement in Vital Signs	Changes from baseline for Pulse	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Respiration Rate measurement in Vital Signs	Changes from baseline for respiration rate in breaths of Vital Signs	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Sitting Systolic Blood Pressure	Changes from baseline for Sitting Systolic Blood Pressure	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Sitting Diastolic Blood Pressure	Changes from baseline for Sitting Diastolic Blood Pressure	Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
The recommended Phase II dose	Determine the Recommended Phase II Dose(mg/㎡) of HF158K1 and provide references for dose selection in future clinical studies.	After the end of the dose Expansion Phase（only Ic）

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HF158K1 pharmacokinetic parameters with Cmax	Maximum plasma concentration (Cmax) after administration of HF158K1	Within 336 hours after the first and second administration
AUC by plasma concentration of whole blood sample	Area under plasma concentration -time curve after dose	Within 336 hours after the first and second administration
Tmax by plasma concentration of whole blood sample	Peak time (Tmax) after dose	Within 336 hours after the first and second administration
T1/2 by plasma concentration of whole blood sample	Elimination half-life (T1/2) after dose	Within 336 hours after the first and second administration
CL by plasma concentration of whole blood sample	Clearance (CL) after dose	Within 336 hours after the first and second administration
Vd by plasma concentration of whole blood sample	Volume of distribution(Vd) after dose	Within 336 hours after the first and second administration
AUClast by plasma concentration of whole blood sample	Ratios of geometric means of AUClast (Area under the plasma concentration-time curve from zero to time of last quantifiable concentration) after dose	Within 336 hours after the first and second administration
The objective response rate(ORR) of HF158K1	ORR is defined as the proportion of participants with complete response or partial response (CR+PR)	ORR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks.
disease control rate (DCR) of HF158K1	DCR is defined as the proportion of participants with complete response stable disease and partial response (CR+PR+SD)	DCR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks.
duration of response(DOR) of HF158K1	For duration of response (DOR), the Kaplan-Meier survival curve will be plotted to analyze their maximum, minimum, median and 95% confidence interval descriptively statistically.	DOR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks.
Analysis of immunogenicity	Immunogenicity analyses related to anti-TL01 antibody will be performed based on IMS(Immunogenicity Analysis Set).	On the first day of the first cycle, on the first day of the fourth cycle, on the 21st day of the eighth cycle

Collaborators and Investigators

• Sponsor: HighField Biopharmaceuticals Corporation
• Investigators: Principal Investigator: MINAL BARVE, Mary Crowley Cancer Research

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Estimated): June 23, 2027
• Study Completion (Estimated): December 23, 2027

Study Registration Dates

• First Submitted: April 20, 2023
• First Submitted That Met QC Criteria: May 6, 2023
• First Posted (Actual): May 17, 2023

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HF158K1-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No